Fig. 6: h-lysoTRAP-mediated clearance of authentic SARS-CoV-2 on human lung organoids.

a Schematic for the construction of human lung organoids and anti-infection experiment on organoid model. Lung cells (isolated from normal lung tissues adjacent to tumors derived from resection surgeries) were seeded into Matrigel containing known growth and regulatory factors to induce lung spheroids. 1 d after inoculation with 100 TCID50 authentic SARS-CoV-2 and treatment with different formulations, the lung spheroids were collected for q-PCR analysis, immunofluorescence analysis and lactate dehydrogenase (LDH) release detection. In these formulations, free EIDD-2801 (molnupiravir) can bind with RNA-dependent RNA polymerase (RdRp) to inhibit SARS-CoV-2 infection and have been FDA-approved specific medicine for COVID-19. Free RBD antibody can bind with the RBD area of S protein of SARS-CoV-2 to inhibit SARS-CoV-2 infection. The concentration of free EIDD-2801 and RBD antibody was selected to match the amount of ACE2 present on the membrane of the h-lysoTRAP. b q-PCR analysis of wild-type SARS-CoV-2 RNA copies in human lung organoids, showing the efficient virion clearance and efficiently inhibited viral infection by h-lysoTRAP in human lung organoids. c Representative immunofluorescence images of wild-type SARS-CoV-2 infection, visualized by S protein expression in human lung organoids. d Relative LDH release from human lung organoids after viral inoculation and formulation treatment. e Representative photos of the organoids after viral inoculation and formulation treatment. f–i Similar data as presented in b–e following infection with Omicron variant. j Principal component analysis showing the viral infection profiles (four infection indices) across eight groups. Each dot represents a human lung organoid; the colors of the dot denote the groups; and the ellipses show the distribution of the groups. k Visualization of indices of viral infection among the eight groups. Data were normalized for plotting. The data in b, d, f, and h represent the mean ± S.D. (n = 3 biologically independent experiments). Statistical significance was calculated using two-tailed one-way ANOVA with multiple comparison tests in b, d, f, and h. Source data were provided in the Source data file.